An Investigational Drug (TPST-1495) in Patients With Familial Adenomatous Polyposis

ConditionsColorectal Carcinoma Familial Adenomatous Polyposis

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorNational Cancer Institute (NCI)

About this trial

This open-label phase II trial tests how well TPST-1495 works in reducing the number of polyps in the small bowel and colon in patients with familial adenomatous polyposis (FAP). FAP is an inherited condition in which numerous polyps (growths that protrude from mucous membranes) form on the inside walls of the colon and rectum. It increases the risk for colon cancer. TPST-1495 binds to specific prostaglandin receptors. TPST-1495 is a dual antagonist of the prostaglandin E2 (PGE2) receptor subtypes EP2 and EP4, while sparing the immune-stimulating EP1 and EP3 receptors. TPST-1495 may help reduce the number of polyps in the small bowel and colon in patients with FAP.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Genetic diagnosis with confirmed APC mutation (clinical CLIA [clinical laboratory improvement amendments] certified lab or research testing)

Obligate carrier

Clinical diagnosis of classic FAP with ≥ 100 colorectal adenomas status post colectomy or a sub-total colectomy and a family history of FAP

Clinical diagnosis of FAP, based on personal and family history. Note: This criterion requires documented review and agreement from either the study chair or the MW consortium lead investigator

Disqualifiers

Use of any other investigational agents ≤ 12 weeks prior to pre-registration

History of gastric or intestinal ulceration due to NSAID therapy

Uncontrolled intercurrent illness or recent surgical procedure that in the opinion of the investigative team would limit compliance with study requirements

History of invasive malignancy ≤ 3 years prior to pre-registration (exception: adequately treated carcinoma of the cervix, carcinoma in situ, or basal or squamous cell carcinomas of the skin)

Trial design

Design model

Single group

Treatments tested in this trial

Biopsy Procedure
Procedure/Surgery
Undergo biopsy
Biospecimen Collection
Procedure/Surgery
Undergo blood sample collection
EP2/EP4 Antagonist TPST-1495
Drug
Given PO
Esophagogastroduodenoscopy
Procedure/Surgery
Undergo EGD
Gastrointestinal Endoscopy
Procedure/Surgery
Undergo GI endoscopy
Questionnaire Administration
Other intervention
Ancillary studies

Treatment groups

38 Participants

are divided into 1 treatment group

Group A: Prevention (TPST-1495)Experimental treatment 6 interventions

Trial outcomes

Primary outcomes

Percent change in duodenal polyp burden

Will be determined based on the sum of diameters from all polyps. Will be assessed by comparing upper gastrointestinal (GI) endoscopies respectively. Will be described using a two-sided 95% confidence interval and examined for difference from zero with a one-side paired t-test.

Time frame

Baseline to 6 months

Incidence of adverse events

Will examine the proportion of patients with grade 2 or 3 adverse events according to the Common Terminology Criteria for Adverse Events version 6.0. Will be summarized as a proportion with a 1-sided 90% confidence interval.

Time frame

Up to 7 months

Secondary outcomes

Percent change in rectal/pouch polyp burden

Will be assessed by comparing the lower GI endoscopies. Results will be presented using summary statistics and corresponding confidence intervals.

Time frame

Baseline to 6 months

Other outcomes

Percent change in immunohistochemical staining levels

Will assess rectal and duodenal tissue samples for COX-2 expression level, beta-catenin, and Ki-67. Mean percent change in immunohistochemical staining levels will be associated with intestinal polyp burden using a scatterplot of the two variables and evaluated using a Spearman rank correlation statistic.

Time frame

Baseline to 6 months

Proteomic profile

Will identify proteins that are statistically significantly differently expressed between patients after treatment. The proteomic profile of serum will be correlated to clinical response to therapy and compared between baseline and end of intervention. No formal statistical inference will be performed. Proteins will be described with summary statistics to assist in planning follow-up studies.

Time frame

Baseline to 6 months

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov

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